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Nucleosome occupancy as a novel chromatin parameter for replication origin functions

Eukaryotic DNA replication initiates from multiple discrete sites in the genome, termed origins of replication (origins). Prior to S phase, multiple origins are poised to initiate replication by recruitment of the pre-replicative complex (pre-RC). For proper replication to occur, origin activation m...

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Detalles Bibliográficos
Autores principales: Rodriguez, Jairo, Lee, Laura, Lynch, Bryony, Tsukiyama, Toshio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5287232/
https://www.ncbi.nlm.nih.gov/pubmed/27895110
http://dx.doi.org/10.1101/gr.209940.116
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author Rodriguez, Jairo
Lee, Laura
Lynch, Bryony
Tsukiyama, Toshio
author_facet Rodriguez, Jairo
Lee, Laura
Lynch, Bryony
Tsukiyama, Toshio
author_sort Rodriguez, Jairo
collection PubMed
description Eukaryotic DNA replication initiates from multiple discrete sites in the genome, termed origins of replication (origins). Prior to S phase, multiple origins are poised to initiate replication by recruitment of the pre-replicative complex (pre-RC). For proper replication to occur, origin activation must be tightly regulated. At the population level, each origin has a distinct firing time and frequency of activation within S phase. Many studies have shown that chromatin can strongly influence initiation of DNA replication. However, the chromatin parameters that affect properties of origins have not been thoroughly established. We found that nucleosome occupancy in G1 varies greatly around origins across the S. cerevisiae genome, and nucleosome occupancy around origins significantly correlates with the activation time and efficiency of origins, as well as pre-RC formation. We further demonstrate that nucleosome occupancy around origins in G1 is established during transition from G2/M to G1 in a pre-RC-dependent manner. Importantly, the diminished cell-cycle changes in nucleosome occupancy around origins in the orc1-161 mutant are associated with an abnormal global origin usage profile, suggesting that proper establishment of nucleosome occupancy around origins is a critical step for regulation of global origin activities. Our work thus establishes nucleosome occupancy as a novel and key chromatin parameter for proper origin regulation.
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spelling pubmed-52872322017-08-01 Nucleosome occupancy as a novel chromatin parameter for replication origin functions Rodriguez, Jairo Lee, Laura Lynch, Bryony Tsukiyama, Toshio Genome Res Research Eukaryotic DNA replication initiates from multiple discrete sites in the genome, termed origins of replication (origins). Prior to S phase, multiple origins are poised to initiate replication by recruitment of the pre-replicative complex (pre-RC). For proper replication to occur, origin activation must be tightly regulated. At the population level, each origin has a distinct firing time and frequency of activation within S phase. Many studies have shown that chromatin can strongly influence initiation of DNA replication. However, the chromatin parameters that affect properties of origins have not been thoroughly established. We found that nucleosome occupancy in G1 varies greatly around origins across the S. cerevisiae genome, and nucleosome occupancy around origins significantly correlates with the activation time and efficiency of origins, as well as pre-RC formation. We further demonstrate that nucleosome occupancy around origins in G1 is established during transition from G2/M to G1 in a pre-RC-dependent manner. Importantly, the diminished cell-cycle changes in nucleosome occupancy around origins in the orc1-161 mutant are associated with an abnormal global origin usage profile, suggesting that proper establishment of nucleosome occupancy around origins is a critical step for regulation of global origin activities. Our work thus establishes nucleosome occupancy as a novel and key chromatin parameter for proper origin regulation. Cold Spring Harbor Laboratory Press 2017-02 /pmc/articles/PMC5287232/ /pubmed/27895110 http://dx.doi.org/10.1101/gr.209940.116 Text en © 2017 Rodriguez et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research
Rodriguez, Jairo
Lee, Laura
Lynch, Bryony
Tsukiyama, Toshio
Nucleosome occupancy as a novel chromatin parameter for replication origin functions
title Nucleosome occupancy as a novel chromatin parameter for replication origin functions
title_full Nucleosome occupancy as a novel chromatin parameter for replication origin functions
title_fullStr Nucleosome occupancy as a novel chromatin parameter for replication origin functions
title_full_unstemmed Nucleosome occupancy as a novel chromatin parameter for replication origin functions
title_short Nucleosome occupancy as a novel chromatin parameter for replication origin functions
title_sort nucleosome occupancy as a novel chromatin parameter for replication origin functions
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5287232/
https://www.ncbi.nlm.nih.gov/pubmed/27895110
http://dx.doi.org/10.1101/gr.209940.116
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